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Government agencies are often required to conduct benefit-cost analyses for major regulatory actions (1). When benefit-cost analysis is consistent with best practices, it provides a systematic and science-based approach for informing policy and regulatory decisions. It has been particularly important for health and environmental regulations. Yet the wide disparity between the quantified benefits in two recent and conflicting regulatory impact analyses (RIAs) related to the U.S. Clean Water Act (CWA) has the potential to undermine the credibility of agencies' benefit-cost analyses. It also highlights the need for a more systematic protocol that ensures the information base is adequate and appropriately applied to support agency analyses and public decision-making. This includes applications in the context of the CWA, which is the focus of an 11 October hearing in the U.S. Supreme Court.